Asthma is an important public health concern affecting more than l4 million people in the United States including over 4.8 million children. Epidemiological studies show a trend toward increasing prevalence and morbidity, but the reasons for these increases remain unclear. Asthma is a chronic disease defined by reversible obstruction of the small airways, inflammation, and increased airway responsiveness to a variety of stimuli: a process that disrupts adequate ventilation of the alveoli causing dyspnea and hypoxia. Existing methods of small airways disease are either indirect or imprecise. Hyperpolarized helium-3 (H3He) gas MR lung imaging is a new technology which allows direct visualization of the lung airspaces, the ventilation and small airway disease, enabling assessment of disease activity at a level that was previously impossible to evaluate. Thus, H3He MR imaging has the potential to provide insight into the pathophysiology of asthma and to contribute to improved clinical management. Preliminary studies with H3He MR have demonstrated ventilation defects in asthmatics, even when they were asymptomatic and had normal lung function tests, and the findings suggest that this new technology is capable of detecting subclinical disease. The goal of the proposed research is to gain a better insight into the H3He MR imaging characteristics in asthmatics (Specific Aim # 1) and to determine how these findings correlate with disease activity and severity (Specific Aim #2). In order to obtain information on the imaging characteristics, we will evaluate the H3He MR imaging findings in populations of symptomatic and asymptomatic asthmatics, using healthy, non-asthmatics as controls. In addition, we will determine in small subgroups of patients how these findings compare to those obtained with two existing lung imaging modalities, nuclear medicine ventilation scanning and computed tomography (CT). To determine the ability of H3He lung MR in assessing disease activity, we will evaluate the imaging changes that occur during tests that provoke (worsen) and treat (improve) asthma. Provocation tests include inhalation of methacholine, exercise, administration of endobronchial allergen and viral inoculation, and treatments include inhaled of p2agonist (albuterol) and steroids (asthmacort). The results of the studies proposed in this research will serve as a foundation for developing future clinical and basic research applications.
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